Method for producing macrocyclic ketones

ABSTRACT

The present invention relates to a novel thermo-isomerization method for rapidly and simply producing macrocyclic ketones of the formula Ia or Ib. 
                 
 
     The macrocyclic ketones are prepared in the gas phase at temperatures above 500° C. rapidly and in a simple manner from alcohols of the formula IIa and IIb directly with a high yield. 
                 
 
     In the formulae Ia, Ib, IIa and IIb, R1-R5, and n have the meanings given in the description.

The present invention relates to a novel thermo-isomerization method forrapidly and simply producing macrocyclic ketones.

Macrocyclic ketones are of considerable importance in perfumery becauseof their musk-like odor properties. In this connection,cyclopentadecanone (Exalton®), 3-methylcyclopentadecanone (muscone),cycloheptadec-9-en-1-one (civettone) and (E/Z)-cyclohexadec-5-en-1-one(Ambretone®, Musk TM II®) in particular are to date of commercialimportance as musk ketones. As is known from the specialist literature,such macrocyclic ketones can be prepared by multistage syntheses whichare essentially based on two basic methods:

-   a) Macrocyclization reactions (for example, the so-called acyloin    condensation of α,ω-diesters with subsequent reduction or the    intramolecular olefin metathesis (ring closure metathesis, RCM)    etc.). Since polymerization processes should be avoided, most    macrocyclization reactions are only carried out using high dilutions    and are therefore too cost-intensive for reactions on an industrial    scale.-   b) Ring expansion reactions which are based either on a multistage    sequence of anellation and fragmentation reactions, or on    sigmatropic [3.3]-rearrangement reactions (e.g. oxy-Cope reaction of    1,2-divinylcycloalkan-1-ols), or also [1.3]-displacement reactions    in the case of 1-vinylcycloalk-3-en-1-ols (W. Thies, P. Daruwala, J.    Org. Chem. 1987, 52, 3798-3806).

Ring expansion reactions by 2 carbon atoms according to the principle ofa [1.3]-displacement reaction are described in numerous scientificarticles (for example in Tetrahedron Lett. 1970, 513-516). In the caseof 1-vinyl-cyloalk-3-en-1-ols with a nine- to thirteen-membered ringsystem and endocyclic, homoallylic double bond in position 3, instead of[3.3]-rearrangement products (ring expansion by four carbon atoms), ringexpansions in the sense of a [1.3]-displacement (ring expansion by twocarbon atoms) was preferentially observed under the thermal conditionsfor oxy-Cope rearrangements. The yield is at most 25% since theelimination of water occurs as an undesired reaction. Significantlybetter yields (50-80%) are described when the vinyl alcohol has beenconverted into the corresponding trimethylsilyl ether prior to heating.The same products were obtained when the rearrangement reaction wascarried out with the corresponding doubly unsaturated potassium alkoxideunder strongly anionic conditions (2 mol equivalent of potassium hydridein HMPA at 25-100° C.).

In J. Am. Chem. Soc. 1974, 964, 200-203, it is expressly pointed outthat both in the case of the trimethylsilyl ether derivative, andparticularly also in the case of the non-derivatized vinyl alcoholitself, an analogous [1.3]-displacement reaction could no longer beobserved at temperatures up to 320° C. as soon as the homoallylicendocyclic double bond (in position 3) was removed. The application ofadditionally forced reaction conditions (reaction temperatures up to420° C.) led in both cases primarily to the formation of alkenes(elimination of water). J. Chem. Soc. 1978, 43, 1050-1057, describesthat no products of a ring expansion could be observed with the use ofanionic rearrangement conditions either, i.e. by treating the vinylalcohol, which has a saturated ring system, with potassium hydride inHMPA for 4 or 24 h at room temperature.

The 1-vinylcyclopropanols, which are structurally related to thevinylcyclopropanes, rearrange irreversibly to give 2-substitutedcyclobutanones when heated to only 100° C. within a short time with a[1.2]-migration. However, if, on the other hand, instead of thevinylcyclopropanols, their trimethylsilyl ether derivatives(1-trimethylsilyloxy-1-vinylcyclopropanes) are heated, then these canagain be converted into cyclopentanones with a [1.3]-migration (J. Am.Chem. Soc. 1973, 95, 5311-5321; and J. Org. Chem. 1981, 46, 506-509).

J. Org. Chem, 1978, 43, 4903-4905 and J. Org. Chem, 1980, 45, 2460-2468describe ring expansion by two carbon atoms also in the case ofspecially functionalized macrocyclic dithiaspiroketone derivatives (e.g.1.5-dithiaspiro[5.12]octa-decan-7-one). This described method cannot beused on relatively small ring systems, such as on cyclododecanone asstarting material.

An object of the present invention is a simple and cost-effective methodfor producing macrocyclic ketones.

Surprisingly, it has been found that, through the thermo-isomerizationmethod according to the invention, macrocyclic ketones of the formula Iaor Ib can be produced in the gas phase at temperatures above 500° C.rapidly and in a simple manner directly with a high yield.

Accordingly, the invention provides in one of its aspects athermo-isomerization method for producing macrocyclic ketones of theformula Ia and Ib

wherein

-   -   R¹, R² and R³ are independently hydrogen or a C₁ to C₆ alkyl        group,    -   R⁴ is hydrogen, a linear or branched C₁ to C₄-alkyl group,    -   n is an integer of 7 to 14, and        in formula Ia, R¹ and R² or R² and R³ can, independently of one        another, form a ring.

The ketones of the formula Ia or Ib ring-extended by two carbon atomsare produced by converting under reduced pressure at 100-300° C. intothe gas phase a macrocyclic tertiary allyl or propargyl alcohol of theformula IIa or IIb

-   -   wherein R¹, R², R³, R⁴, and n have the same meanings as above,        and R⁵ is either hydrogen, trialkylsilyl, or an alkali metal        cation,    -   and then heating the macrocyclic tertiary allyl or propargyl        alcohol of the formula IIa or Iib, converted into the gas phase,        at temperatures of 500 to 700° C., and    -   hydrolysis of the trialkyl silyl ether into the corresponding        ketone of the formula Ia or Ib, if R⁵ is a trialkylsilyl.

The size of the ring system is therefore described by n. If n=7,10-membered cyclic ketones are obtained from 8-membered cyclic alcohols.In the case of n=14, 17-membered cyclic ketones can accordingly beobtained from 15-membered cyclic alcohols.

C₁-C₆ Alkyl is, for example, methyl, ethyl, propyl, isopropyl, butyl,sec- or tert-butyl, pentyl or hexyl, where methyl is particularlypreferred.

Depending on the nature of the substituents on the vinyl group of thetertiary cyclic alcohol of the formula IIa used as starting material,thus the substituents are not hydrogen, the described method allows thesimultaneous production of ring-expanded and additionally regioselectivesubstituted macrocyclic ketones. The positions of the substituents inthe macrocyclic ketones are located as shown in formula Ia on the twosuccessive carbon atoms adjacent to the carbon atom of the carbonylgroup (regarded as C(1)) and distribute themselves in the following way:R¹ is on the carbon atom directly adjacent to the carbonyl group (thusin the α-position) on C(2) and both R² and R³ are each on the same ringhalf of the macrocyclic ketone at a distance of two carbon atoms fromthe carbonyl group (thus in the β-position) on C(3), directly adjacentto C(2) . If, in the method described, instead of tertiary cyclic allylalcohols, corresponding macrocyclic propargyl alcohols of the formulaIIb are used, then macrocyclic ketones are obtained, which contain adouble bond in direct conjugation to the carbonyl group (α,β-unsaturatedketones). If there is an additional substituent R⁴ on the ring system ofthe cyclic alcohol (thus R⁴ is not hydrogen) regioisomeric ring-extendedmacrocyclic ketones can additionally be obtained, depending on whichhalf of the cyclic system the two carbon atoms of the original vinylgroup of the starting material are incorporated according to the methoddescribed above. This naturally also applies when R⁴ represents two ormore substituents.

Using the described thermo-isomerization process, it is possible toproduce, from tertiary cyclic allyl or propargyl alcohols, macrocyclicketones which can in turn be converted efficiently and in a simplemanner by known methods into cyclic tertiary allyl or propargylalcohols, which can in turn be used as starting materials in thedescribed thermo-isomerization method. The described process thereforeadditionally offers, by repetition of the process, the options ofproducing, by iteration, in each case also the macrocyclic ketonesring-expanded by four, six, eight, etc. carbon atoms, in which case onlytwo synthesis stages are required per repeat cycle.

In the same way, the described method can also be used for the analogousetherified derivatives of the parent macrocyclic tertiary alcohols, forexample, trialkyl silyl ethers, in particular for trimethylsilyl ethers(when thus R⁵ in formula IIa or IIb represents a trimethylsilyl group),where then, in an analogous manner, firstly, however, in each casemixtures of the corresponding ring-expanded cyclic trimethylsilyl enolethers are obtained. Hydrolysis of these trimethylsilyl enol ethermixtures then likewise leads again to the same ketones which can beobtained from the corresponding parent alcohols in a direct manner,without prior derivatization by a suitable silyl group and thus withoutthe additionally required hydrolysis stage.

By carrying out the thermo-isomerization in the gas phase, the methodaccording to the invention can take place without the use of solvent andthus in a manner which respects environmental protection, if thestarting material is vaporized directly into the gas phase and passed tothe reactor unit. Expedient design of the apparatus additionally allowsthe described thermo-isomerization method to be carried out continuouslyand thus potentially also permits process automation. In the scientificspecialist literature there are many descriptions of different apparatusfor carrying out very diverse analogous chemical conversion processes inthe gas phase using temperatures of up to about 1000° C. (gas-phase flowthermolysis or short-term vacuum pyrolysis apparatuses).

The method according to the invention for producing macrocyclic ketonesis based on the thermo-isomerization of tertiary macrocyclic allylalcohols or propargyl alcohols in the gas phase at temperatures of from500 to 700° C. To carry out the method according to the invention, thealcohol used as starting material is either initially introduced in avaporization unit, or is added via a metering device, such as a meteringor spray pump, from a storage vessel, preferably either in undilutedform or else in dissolved form in a suitable inert solvent (such as, forexample, xylene) in a continuous manner and heated, under reducedpressure depending on the boiling point of the starting material used totemperatures in the range from about 100-300° C., preferably in therange from 120-250° C. and thereby converted into the gas phase. Thealcohol preheated in the vaporization unit is then passed into the gasphase, optionally also using a regulatable inert gas stream, where theinert gas can, for example, be nitrogen, argon or helium, and, atreduced pressure, through a suitably dimensioned and appropriatelyshaped reactor unit which is heated to temperatures between 500 and 700°C., where the macrocyclic tertiary allyl or propargyl alcohol usedaccording to the present description of the thermo-isomerization processaccording to the invention is converted into the correspondingmacrocyclic ketone.

The reactor unit is generally expediently tubular in shape, and ispreferably made of an inert material which is thermostable and does notinterfere with the course of the isomerization reaction, for example,certain types of high-melting glass. It can be arranged horizontally orvertically or at any desired incline, and it can be heated independentlyof the vaporization unit in a generally known manner, for example, usingan electric heating mantle. The temperature range required for thedescribed thermo-isomerization method depends simultaneously on a numberof factors, for example, the prevailing pressure within the reactor, theconfiguration and dimensions of the reactor vessel, the size of theinert-gas stream (flow) and the rate of addition and rate ofvaporization of the starting material or of its solutions, and on thesolvent. It is preferably in the range of from 500 to 700° C. Belowabout 450° C. the thermo-isomerization process is so slow that primarilyunchanged starting material and in some instances dehydration productsare found, whereas at temperatures above 700° C. decomposition productsand undesired secondary reactions are observed to an increasing degree.The preferred temperature range for as complete as possible a conversionof the starting materials used in the described thermo-isomerizationmethod is directly dependent on the stated individual reactor parametersand often is above 550° C., particularly optimally in the range from570° C.-670° C., particularly when the process is carried out withoutsolvents with a gentle inert gas stream or in a high vacuum withoutinert gas stream and without a filler packing. Preferably, the describedthermo-isomerization process is carried out at reduced pressure,particularly advantageously at a vacuum in the range from about 1 to 10mbar (1-10 hPa), in any case expediently below the saturated vaporpressure of the alcohol used as starting material, but the desiredproduct formation can be observed in the inert-gas stream also at a lessgreatly reduced pressure, for example, that obtained by using awater-jet vacuum or a laboratory membrane vacuum pump. The pressure inthe apparatus and thus at the same time the contact time in the reactorunit can additionally be influenced by the regulation of the inert-gasstream, or during injection of liquid starting materials, through therate of addition or in the case of initially solid starting materials,through the rate of vaporization.

In the downstream condenser unit, the gaseous reaction products obtainedby the thermo-isomerization method are cooled to room temperature orbelow by means of a suitable medium by known methods and in so doingliquefied again (or in individual cases resublimed) and then collectedin a receiver. An outlet valve on the receiver and a further valve (tap)on the collecting container which can be detached from the receiverpermits, in accordance with the Normag-Thiele attempt, the collectionand the removal at least of the liquid reaction products also undercontinuing reduced pressure within the described thermo-isomerizationapparatus, in particular in the vaporization, reactor and condenserunit, meaning that a continuous permanent operation of the apparatus canalso be ensured. The reduced pressure in the apparatus is generated by avacuum-pump unit with suitable suction capacity, particularlyadvantageously by means of a high-vacuum pump. It is possible to connectbetween vacuum pump and apparatus further cooling traps a suitablecooling medium to receive readily volatile by-product components.

Using the method according to the invention, the following novelcompounds have been produced:

-   -   2-methylcyclotetradecanone, 3-methylcycloheptadecanone,        5-methylcycloheptadecanone, 3-methylcycloheptadecanone,        4-ethylcyclotetradecanone, 3,4-dimethylcyclotetradecanone.

The tertiary macrocyclic allyl alcohols of the formula IIa required asstarting materials for the thermo-isomerization process can be producedreadily by known methods, for example preferably by the addition ofsuitable organometallic-alkenyl compounds, such as magnesium orlithium-1-alkenyls on to the corresponding macrocyclic ketones. By knownmethods yields of up to 70% of macrocyclic allyl or propargyl alcoholsare obtained by the addition of common vinyl Grignard reagents, such as,vinylmagnesium chloride or vinylmagnesium bromide, or e.g. also ofcorresponding 1- or 2-substituted vinyl-Grignard compounds ormetalloalkynide derivatives, as are shown as substituents on C(1) of thetertiary macrocyclic alcohols of the formula IIa, and where R¹ to R³have the meanings given in the description, are, for macrocyclicketones.

Better yields of macrocyclic allyl alcohols of the formula IIa, mostlyin the region around or also above about 90% can be obtained bytransferring a precomplexation method to macrocyclic ketones. This canbe achieved with catalytic or substoichiometric or stoichiometricamounts of an anhydrous Lewis acid, such as, of cerium trichloride(CeCl₃) at temperatures in the range from about 0-40° C., where improvedyields of tertiary allyl alcohols were obtained during the subsequentaddition of the organometallic-alkenyl used. The addition of from 1.01to about 2 mol equivalents, preferably from 1.5 to 1.8 mol equivalentsof the organometallic-alkenyl solution in absolute THF to the suspensionof the macrocyclic ketone precomplexed in the described manner, usuallyproceeds with noticeable heat of reaction and therefore advantageouslyis conducted such that the rate of the addition is chosen depending onthe existing cooling capacity of the reactor system such that thetemperature of the precooled reaction mixture does not exceed 30 toabout 40° C. The temperature is then maintained, with stirring, forabout a further 10 to 120 minutes at 35 to 40° C., and, after monitoringthe course of the reaction, for example by gas chromatography of thereaction mixture, where necessary 0.1 to 0.2 mol equivalents of thealkenyl or alkynyl compound is again added for as complete as possible aconversion of the ketone used. The tertiary macrocyclic allyl orpropargyl alcohol obtained following hydrolysis of the reaction mixtureis either purified by distillation in a high vacuum or byrecrystallization or chromatography, or else used in the form of thecrude product directly for subsequent thermo-isomerization as startingmaterial.

Using the above-described method it was possible to produce thefollowing novel tertiary macrocyclic allyl alcohols of the formula IIaor propargyl alcohols of the formula IIb required for thethermo-isomerization process as starting material:

-   -   1-vinyl-1-cycloundecanol    -   1-vinyl-1-cyclotridecanol    -   1-vinyl-1-cyclotetradecanol    -   1-vinyl-1-cyclopentadecanol    -   (syn/anti)-2-methyl-1-vinyl-1-cyclododecanol    -   (syn/anti)-3-methyl-1-vinyl-1-cyclopentadecanol    -   (E/Z)-1-(1-propen-1-yl)cyclododecanol    -   (E/Z)-1-(1-propenyl)cyclotridecanol    -   (E/Z)-1-(1-propenyl)cyclotetradecanol    -   (E/Z)-1-(1-propen-1-yl)cyclopentadecanol    -   1-(1-methylethenyl)cycloundecanol    -   1-(2-methyl-1-propenyl)cyclododecanol    -   (E/Z)-1-(2-buten-2-yl)cyclododecanol    -   1-ethynylcyclotridecanol    -   1-(1-propynyl)dodecanol    -   (E/Z)-1-(trimethylsilyloxy)-1-(1-propenyl)cyclododecanol).

EXAMPLES

I. Alkenyl and 1-alkynyl Grignard Reactions

a) Drying of cerium trichloride:

100 g of cerium(III) chloride heptahydrate (Fluka) (0.268 mol) was driedwith continuous rotation in a Büchi Kugelrohr oven in a high vacuum byfirstly heating for 5-6 h at an air bath temperature of 70-80° C., thenfor 3-4 h at 110-120° C. and finally overnight (about 12 h) at 150-160°C. The eliminated water was collected in cool traps (liquid nitrogencooling), these were changed a number of times until finally no morecondensation was observed. After thawing, the liquid content of the cooltraps was collected and thus finally about 34 ml of water and 65 g ofdried pulverulent cerium(III) chloride were obtained. This wastransferred to a storage vessel under an inert gas atmosphere and storedunder an argon atmosphere. Even after storage for several months at roomtemperature, no loss in activity for the Grignard reactions describedbelow was found.

b) Precomplexation of the ketone (typical, generalizable procedure):

36.4 g of cyclododecanone (0.2 mol) was suspended together with 5 g ofanhydrous CeCl₃ (0.02 mol, 0.1 mol equiv.) at room temperature in 100 mlof absolute THF and vigorous stirred under an inert-gas atmosphere for 1to 2 hours until a whitish to intensively yellow homogeneous suspensionof partially gel-like consistency was obtained.

1. Vinyl Grignard reaction (typical, generalizable procedure):

1.1 1-Vinyl-1-cyclododecanol from cyclododecanone:

To the suspension of the ketone activated by precomplexation with CeCl₃was added 320 ml of a 1-molar solution of vinylmagnesium bromide in abs.THF (corresponding to about 0.32 mol of vinylmagnesium bromide, about1.6 mol equiv.) within about 5 min with stirring such that, withtemporary use of a cooling bath (ice bath), the temperature inside thereaction vessel did not exceed the temperature range from 35-40° C.After the exothermic reaction had subsided, the now grayish-greenreaction mixture was stirred for about a further 30 min at 35-40° C.,and the course of the reaction was monitored by gas chromatographicanalysis. Depending on the activity of the cerium(III) chloride used,this usually reveals a starting material conversion significantly above70% already just after 15 minutes, where then, if need be, stillincompletely reacted ketone can be reacted by the addition of furtherabout 0.1 to 0.2 mol equivalents of vinylmagnesium bromide (above 80%conversion).

Work-up: The reaction mixture was left to cool to room temperature andwas poured it on to 1 l of iced water, adding a layer of the extractant(toluene or TBME) and slowly admixed, with stirring, with anapproximately 5-10% strength aqueous hydrochloric acid solution untilthe slime- or gel-like consistency of the mixture had disappeared (aboutpH 3 or below) and, with the appearance of a yellow to brownishcoloration, a clear phase boundary could finally be recognized. Theaqueous phase was removed and the organic phase was washed a number oftimes, firstly with water, then with sodium hydrogencarbonate solutionor with about 5% strength NaOH solution, then again with water, conc.aqueous NaCl solution and finally dried over sodium sulfate or magnesiumsulfate. After the extractant had been evaporated under reducedpressure, the crude product obtained was 41.3 g of1-vinyl-1-cyclododecanol (crude yield 97% of theory, GC purity>86%,comprises about 12-14% cyclododecanone) was obtained as a slightlyyellowish solid. This was either used directly for the subsequentthermo-isomerization or purified beforehand either by Kugelrohrdistillation at a high vacuum and recrystallization from hexane/TBME(95:5, v:v) or by chromatography over silica gel (hexane:TBME 9:1):colorless, wax-like solid with melting point 53° C.

¹H-NMR (300 MHz, CDCl₃): 5.98 (dd, J=10.8, 17.4 Hz, 1 H), 5.20 (dd,J=1.4, 17.4 Hz, 1 H), 5.01 (dd, J=1.4, 10.8 Hz, 1 H), 1.9-1.2 (m, 23 H).¹³C-NMR (75 MHz, CDCl₃): 145.3 (d); 111.0 (t); 75.3 (s); 34.6 (2), 26.3(2), 25.9, 22.5 (2), 22.1 (2), 19.5 (2) (6 t).EI-MS (GC/MS): 210.2 (2,M⁺°), 192.2 (50, M−18), 77.7 (98), 67 (100), 55 (97).

In an analogous manner, the following tertiary macrocyclic allylalcohols were also prepared, by way of example, from the correspondingketones by the addition of vinylmagnesium bromide:

1.2. 1-Vinyl-1-cyclooctanol from cyclooctanone:

Yield 94%, GC purity>90%

¹H-NMR (300 MHz, CDCl₃): 6.01 (dd, J=10.8, 17.4 Hz, 1 H); 5.23 (dd,J=1.3, 17.4 Hz, 1 H); 5.13 (dd, J=1.3, 10.8 Hz, 1 H); 1.92-1.25 (m, 15H). ¹³C-NMR (75 MHz, CDCl₃): 145.8 (d); 111.1 (t); 75.1 (s); 36.2 (2),28.1 (2), 24.6, 21.9 (2) (4 t).EI-MS (GC/MS): 154 (2, M⁺°), 136 (100,M—H₂O).

1.3. 1-Vinyl-1-cyclodecanol from cyclodecanone:

¹H-NMR (300 MHz, CDCl₃): 5.99 (dd, J=10.8, 17.4 Hz, 1 H); 5.21 (dd,J=1.4, 17.4 Hz, 1 H); 5.01 (dd, J=1.4, 10.8 Hz, 1 H); 1.85-1.25 (m, 19H). ¹³C-NMR (75 MHz, CDCl₃): 145.5 (d); 110.9 (t); 76.2 (s); 34.2 (2),26.7, 26.1 (2), 23.5 (2), 21.1 (2) (4 t).EI-MS (GC/MS): 182 (1, M⁺°),164 (42, M—H₂O), 149 (31), 135 (42), 79 (95), 68 (100), 55 (68).

1.4. 1-Vinyl-1-cycloundecanol from cycloundecanone:

Yield 84%.

¹H-NMR (300 MHz, CDCl₃): 5.98 (dd, J=10.8, 17.4 Hz, 1 H); 5.20 (dd,J=1.4, 17.4 Hz, 1 H); 5.01 (dd, J=1.3, 10.8 Hz, 1 H); 1.76-1.20 (m, 21H). ¹³C-NMR (75 MHz, CDCl₃): 145.4 (d); 111.1 (t); 75.8 (s); 36.2, 27.0,25.9, 25.4, 21.1 (5 t, je 2 CH₂). EI-MS (GC/MS): 196.1 (1, M⁺°), 178(15, M—H₂O), 169 (18), 149 (17), 135 (20), 111 (55), 97 (80), 83 (100),70 (95), 55 (100).

1.5. 1-Vinyl-1-cyclotridecanol from cyclotridecanone:

Yield 84%, content according to GC 92%.

¹H-NMR (300 MHz, CDCl₃): 5.98 (dd, J=10.8, 17.4 Hz, 1 H); 5.21 (dd,J=1.4, 17.4 Hz, 1 H); 5.01 (dd, J=1.4, 10.8 Hz, 1 H); 1.65-1.2 (m, 25H). ¹³C-NMR (75 MHz, CDCl₃): 145.4 (d); 111.1 (t); 75.1 (s); 37.4, 27.8,26.6, 25.4, 25.3, 20.9 (5 t). EI-MS (GC/MS): 224 (1, M⁺°), 206 (100,M—H₂O).

1.6. 1-Vinyl-1-cyclotetradecanol from cyclotetradecanone:

Yield 98%.

¹H-NMR (300 MHz, CDCl₃): 5.99 (dd, J=10.8, 17.4 Hz, 1 H); 5.22 (dd,J=1.4, 17.4 Hz, 1 H); 5.03 (dd, J=1.4, 10.8 Hz, 1 H); 1.6-1.2 (m, 27 H).¹³C-NMR (75 MHz, CDCl₃): 145.4 (d); 111.3 (t); 75.0 (s); 37.2 (2), 26.43(2), 26.38, 25.9, 24.0, 23.5, 20.3 (7 t). EI-MS (GC/MS): 224 (1, M⁺°),206 (100, M—H₂O).

1.7. 1-Vinyl-1-cyclopentadecanol from cyclopentadecanone:

Yield 92%.

¹H-NMR (300 MHz, CDCl₃): 5.97 (dd, J=10.8, 17.4 Hz, 1 H); 5.22 (dd,J=1.4, 17.4 Hz, 1 H); 5.03 (dd, J=1.4, 10.8 Hz, 1 H); 1.6-1.2 (m, 29 H).¹³C-NMR (75 MHz, CDCl₃): 145.4 (d); 111.3 (t); 75.0 (s); 37.2 (2), 26.43(2), 26.38, 25.9, 24.0, 23.5, 20.3 (7 t). EI-MS (GC/MS): 252.1 (1, M⁺°),234 (10, M—H₂O).

1.8. (syn/anti)-2-Methyl-1-vinyl-1-cyclododecanol from(RIS)-2-methylcyclodecanone:

Yield 98%.

¹H-NMR (300 MHz, CDCl₃): 5.93/5.88 (dd, J=10.8, 17.3 Hz, 1 H); 5.24/5.23(dd, J=1.6, 17.3 Hz, 1 H); 5.08/5.06 (dd, J=1.6, 10.8 Hz, 1 H); 2.1-1.1(m, 22 H), 0.85/0.81 (d, J=6.6 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃):144.7/142.4 (d); 112.2/111.0 (t); 78.0/77.9 (s); 38.4/35.9 (t);35.5/34.4 (d); 28.7, 26.8, 26.5, 26.3 (2), 25.0, 24.8, 23.4, 23.1, 23.0,22.9, 22.8 (2), 22.7, 22.2, 22.1, 20.4, 18.4 (18 t); 14.6/13.6 (q).EI-MS (GC/MS): 224.1 (7, M⁺°), 209(9, M−15), 206 (6, M−18).

1.9. (syn/anti)-3-Methyl-1-vinyl-1-cyclopentadecanol from rac.3-methylcyclopentadecanone:

Yield 93%

¹H-NMR (300 MHz, CDCl₃) of A: 5.93 (dd, J=10.7, 17.3 Hz, 1 H); 5.18 (dd,J=1.3, 17.3 Hz, 1 H); 5.0 (dd, J=1.3, 10.7 Hz, 1 H); 1.8-1.0 (m, 28 H),0.99 (d, J=6.6 Hz, 3 H); of B: 5.97 (dd, J=10.8, 17.4 Hz, 1 H); 5.21(dd, J=1.4, 17.4 Hz, 1 H); 5.0 (dd, J=1.4, 10.8 Hz, 1 H); 1.8-1.0 (m, 28H), 0.88 (d, J=6.5 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃) of A (main isomer):146.0 (d); 110.9 (t); 75.7 (s); 46.0, 38.9, 37.2 (3 t), 27.0 (d) 22.2(q), 26.6 (t); of B: 146.0 (d); 110.9 (t); 75.7 (s); 46.0, 38.9, 37.2 (3t), 27.0 (d) 22.2 (q), 26.6 (t); of A or B: 27.4, 27.2, 27.1, 27.0,26.9, 26.7, 26.6, 26.4, 26.3, 26.2, 26.0, 25.9 (2), 25.8, 25.0, 24.9 (16t); of A: 22.2 (q), 22.6 (t); of B: 21.7 (q), 21.2 (t).

EI-MS (GC/MS) of A: 266 (2, M⁺°), 248 (28, M—H₂O), 233 (7), 219 (11),121 (40),107 (55), 94 (58), 67 (83), 55 (100); of B: 266 (4, M⁺°), 248(100, M—H₂O), 233 (12), 219 (16), 121 (30), 107 (42), 67 (55), 55 (100).

1.10. (syn/anti)-2-Ethyl-1-vinyl-1-cyclododecanol from(R/S)-2-ethylcyclodecanone:

Yield 98%.

¹H-NMR (300 MHz, CDCl₃) of the diastereoisomer mixture: 5.93/5.88 (dd,J=10.8, 17.3 Hz, 1 H); 5.24/5.23 (dd, J=1.6, 17.3 Hz, 1 H); 5.08/5.06(dd, J=1.6, 10.8 Hz, 1 H); 2.1-1.1 (m, 24 H), 0.97/0.91 (2t, J=7.3 Hz, 3H). ¹³C-NMR (75 MHz, CDCl₃): 144.7/143.0 (d); 111.7/110.7 (t); 78.7/78.6(s); 43.0/41.4 (d); 39.2, 37.0, 28.2, 26.7, 26.6, 25.9, 25.7 (2), 24.8,23.8, 23.7, 23.6, 23.5, 23.4, 23.2, 23.1, 23.0, 22.8, 22.4, 22.2, 20.6,18.6 (22 t); 14.7/13.2 (q).

2. Grignard reactions with alkyl-substituted vinyl halides:

a) 1-Propenyl-Grignard reactions

2.1. (E/Z)-1-(1-Propen-1-yl)cyclododecanol:

The solution of the Grignard reagent prepared beforehand from 3.9 g ofmagnesium (0.16 mol) and 20.6 g of 1-bromo-1-propene (E/Z mixture, 0.17mol) in 160 ml of absolute THF by customary methods were added, withstirring and via cannulae, to 18.2 g of cyclododecanone (0.1 mol) whichhad been precomplexed beforehand analogously to Example Ib of the abovedescription with 2.5 g of CeCl₃ (10 mmol, 0.1 mol equiv.), the procedurecorresponding to that described in Example 1.1. Crude yields of(E/Z)-1-(1-propenylcyclododecanol): 21 g (94%), wax-like solid, GCpurity 92% (comprises about 6% cyclododecanone). Purification byrecrystallization from hexane:ether 95:5 (v:v). Separation of the E- andZ-isomer by column chromatography (silica gel, hexane, ether, 9:1),whereas the less polar Z-isomer (white solid) eluted first:

Z-Isomer: ¹H-NMR (300 MHz, CDCl₃): 5.50-5.36 (m, 2 H; analysis at 600MHz reveals 5.46 (dq, J=11.8 Hz, 7.0 Hz), 5.39 dq (J=11.8 Hz, 1.6 Hz)),1.87 (dd, J=7 Hz, 1.6 Hz, 3 H), 1.75-1.55 (m, 4 H), 1.49-1.2 (m, 19 H).¹³C-NMR (75 MHz, CDCl₃): 136.4 (d); 125.8 (d); 76.1 (s); 35.8 (2); 26.5(2), 26.1, 22.6 (2), 22.3 (2), 19.7 (2) (6 t); 14.5 (q).

E-Isomer (colorless, wax-type solid): ¹H-NMR (300 MHz, CDCl₃): 5.68-5.55(m, 2H; analysis at 600 MHz reveals 5.64 (dq, J=15.6, 6 Hz), 5.59 (dq,J=15.6, 1.1 Hz)), 1.69 (dd, J=6, 1 Hz, 3 H), 1.68-1.22 (m, 23 H).¹³C-NMR (75 MHz, CDCl₃): 138.4 (d); 122.2 (d); 74.9 (s); 35.0 (2); 26.5(2), 25.9, 22.6 (2), 22.2 (2), 19.6 (2) (6 t); 17.7 (q).

In an analogous manner, the following tertiary macrocyclic allylalcohols were produced, also by way of example, from the correspondingketone by the addition of (E/Z)-1-(1-propenyl)magnesium bromide:

2.2. (E/Z)-1-(1-Propenyl)cyclotridecanol from cyclotridecanone:

Yield 82%.

Z-Isomer (white solid) : ¹H-NMR (300 MHz, CDCl₃): 5.50-5.39 (m, 2 H),1.87 (dd, J=6.5, 1.8 Hz, 3 H), 1.70-1.60 (m, 4 H), 1.35 (br. s-type m,21 H). ¹³C-NMR (75 MHz, CDCl₃): 136.5 (d); 125.7 (d); 76.0 (s); 38.8(2); 27.8 (2), 26.6 (2), 25.4 (4), 21.1 (6 t); 14.3 (q).

E-Isomer (colorless, viscous oil, main isomer): ¹H-NMR (300 MHz, CDCl₃):5.65-5.55 (m, 2H), 1.69 (d, J=5, 3 H), 1.68-1.46 (m, 4 H), 1.35 (br.s-type m, 21 H). ¹³C-NMR (75 MHz, CDCl₃): 138.2 (d); 122.2 (d); 74.6(s); 37.8 (2); 27.9 (2), 26.7 (2), 25.5 (2) 25.4 (2), 21.0 (2), (6 t);17.7 (q).

2.3. (E/Z)-1-(1-Propen-1-yl)cyclotetradecanol from cyclotetradecanone:

Yield 93%.

Z-Isomer (white solid): ¹H-NMR (300 MHz, CDCl₃): 5.52-5.39 (m, 2 H;analysis at 600 MHz reveals 5.46 (dq, J=12, 6.7 Hz), 5.43 dq (J=12, 1.3Hz)), 1.87 (dd, J=5.6 Hz, 1.9 Hz, 3 H), 1.68-1.51 (m, 4 H), 1.39-1.18(m, 21 H). ¹³C-NMR (75 MHz, CDCl₃): 136.6 (d); 125.7 (d); 75.9 (s); 38.8(2); 27.8 (2), 26.5 (2), 26.4, 26.0 (2), 23.5 (2), 20.4 (2) (7 t); 14.3(q).

E-Isomer (main isomer, colorless, viscous oil, which graduallysolidifies upon standing to give a solid): ¹H-NMR (300 MHz, CDCl₃):5.71-5.56 (m, 2H; analysis at 600 MHz reveals 5.65 (dq, J=16 Hz, 6 Hz),5.59 dq (J=16 Hz, 1.1 Hz)), 1.70 (d, J=5 Hz, 3 H), 1.63-1.18 (m, 27 H).¹³C-NMR (75 MHz, CDCl₃): 138.5 (d); 122.4 (d); 74.6 (s); 37.5 (2); 26.5(2), 26.4, 26.0 (2), 24.0 (2) 23.5 (2), 20.4 (2), (7 t); 17.7 (q).

2.4. (E/Z)-1-(1-Propen-1-yl)cyclopentadecanol from cyclopentadecanone:

Yield 90%.

E/Z-Isomer mixture: ¹H-NMR (300 MHz, CDCl₃): 5.68-5.44 (m)/5.50-5.39 (m,2 H); 1.87 (d, J=5.8 Hz)/1.69 (d, J=5.2 Hz, 3 H), 1.67-1.20 (m, 29 H).¹³C-NMR (75 MHz, CDCl₃): 138.4/136.5 (d); 125.8/122.5 (d); 75.9/74.6(s); 39.5/38.8; 26.9, 26.6 (3), 26.24, 26.20, 21.9, 21.8; 17.7/14.3 (q).

b) 2-Propenyl-Grignard reactions (typical, analogous procedure):

2.5. 1-(1-Methylethenyl)cyclododecanol from cyclododecanone

14.5 g of cyclododecanone (80 mmol), precomplexation with 1 g of CeCl₃(4 mmol=0.05 mol equiv.); about 100 mmol of 1-propen-2-ylmagnesiumbromide (freshly prepared from 2.43 g of magnesium and 14 g of2-bromo-1-propene in THF). After 2 h, about 15% starting materialaccording to GC. Following customary work-up and Kugelrohr distillationin a high vacuum, 16.8 g (93%) of colorless, viscous oil was obtained,which gradually solidified from standing (comprises 15% cyclododecanoneaccording to GC). Recrystallization twice from hexane at −15° C. gave12.9 g (72%) of a white crystalline solid.

¹H-NMR (300 MHz, CDCl₃): 4.84-4.82 (m, 2 H); 1.79 (d, 0.6 Hz, 3H), 1.63(m_(c), 4 H); 1.4-1.2 (m, 19 H). ¹³C-NMR (75 MHz, CDCl₃): 150.6 (s);110.4 (t); 76.8 (s); 32.8 (2), 26.5 (2), 26.1, 22.5 (2), 22.2 (2), 19.9(2) (6 t); 18.8 (q).

EI-MS (GC/MS): 224.1 (4, M⁺°), 206.1 (28, M—H₂O), 55.0 (100).

2.6. 1-(1-Methylethenyl)cycloundecanol from cycloundecanone:

Yield 88%.

¹H-NMR (300 MHz, CDCl₃): 4.83 (d, J=16.4 Hz, 2 H); 1.78 (d, 0.6 Hz, 3H), 1.74-1.70 (m, 4 H); 1.64-1.2 (m, 17 H). ¹³C-NMR (75 MHz, CDCl₃):150.6 (s); 110.1 (t); 77.3 (s); 34.1 (2), 27.1 (2), 26.1(2), 25.4 (2),21.5 (2), (5 t); 18.8 (q).

EI-MS (GC/MS): 210.1 (1, M⁺°), 192.0 (95, M—H₂O), 148.8 (100).

c) Grignard reactions with alkyl-disubstituted vinyl halides:

2.7. 1-(2-Methyl-1-propenyl)cyclododecanol from cyclododecanone:

3.0 g of cyclododecanon (16.5 mmol), precomplexation with 1 g of CeCl₃(4 mmol=0.25 mol equiv.); about 25 mmol of2-methyl-1-propen-1-ylmagnesium bromide (freshly prepared from 0.6 g ofmagnesium and 3.5 g of 1-bromo-2-methyl-1-propene (isocrotyl bromide) inTHF). After 2 h, about 3% of starting material according to GC.Customary work-up and Kugelrohr distillation in a high vacuum gave 2.9 g(74%) of colorless, viscous oil, which gradually solidified on standingto become wax-like.

¹H-NMR (300 MHz, CDCl₃): 5.22 (br. s-type m, 1 H); 1.87 (d, J=1.2 Hz, 3H), 1.69 (d, J=1.2 Hz 3 H); 1.63-1.5 (m, 4 H); 1.48-1.2 (m, 19 H).¹³C-NMR (75 MHz, CDCl₃): 134.2 (s); 130.7 (d); 75.1 (s); 36.0 (2) (t),27.2 (q); 26.4 (2), 25.9, 22.5 (2), 22.2 (2), 19.6 (2) (5 t); 18.9 (q).

EI-MS (GC/MS): 238.1 (8, M⁺°), 220.1 (45, M—H₂O), 96.0 (100).

2.8. (E/Z)-1-(2-Buten-2-yl)cyclododecanol from cyclododecanone:

9.1 g of cyclododecanone (50 mmol), precomplexation with 2 g of CeCl₃ (8mmol=0.16 mol equiv.); about 80 mmol of (E/Z)-2-buten-2-ylmagnesiumbromide (freshly prepared from 2.0 g of magnesium and 10.8 g of1-bromo-2-methyl-1-propene in THF). After 2 h, about 30% startingmaterial as well as 2 main products (31 and 15%, respectively) accordingto GC. Customary work-up gave 11.3 g (95%) of a slightly yellowishwax-like solid. Recrystallization twice from hexane at −20° C. gives 4.3g (36%) of colorless crystals of an E/Z-isomer mixture (about 4:1).

Separation of the isomers by column chromatography over silica gel(hexane/TBME 94:6):

¹H-NMR (300 MHz, CDCl₃) Isomer A (eluted first, colorless crystals):5.37 (dq, J=7.3, 1.3 Hz, 1 H), 1.84 (dd, J=7.3, 1.3 Hz, 3 H), 1.72-1.70(m, 7 H), 1.45-1.25 (m, 19 H). ¹³C-NMR (75 MHz, CDCl₃): 140.9 (s), 122.8(d), 77.8 (s), 34.6 (2), 26.4 (2), 26.0 (3 t), 23.2 (q), 22.4 (2), 22.1(2), 19.6 (3 t), 15.1 (q).

¹H-NMR (300 MHz, CDCl₃) Isomer B (eluted later, colorless crystals):5.43 (m_(c), 1 H), 1.67 (m, 3 H), 1.62-1.55 (m, 7 H), 1.45-1.1 (m, 19H). ¹³C-NMR (75 MHz, CDCl₃): 140.8 (s), 118.2 (d), 77.1 (s), 32.7 (2),26.3 (2), 26.0, 22.4 (2), 22.1 (2) (6 t), 13.3 (q), 11.6 (q).

2.9. (E/Z)-2-Methyl-1-(1-propen-1-yl)cyclododecanol from2-methylcyclododecanone:

Isomer mixture: characteristic signals in ¹³C-NMR (75 MHz, CDCl₃):137.4, 135.4, 135.1, 133.2, 125.7 ,124.8, 122.8, 121.4 (8 d); 79.6,79.2, 77.3, 77.2 (4 s); 37.1, 36.2, 35.6, 34.8 (4 d); 14.5, 14.4, 13.9,13.5 (4 q). EI-MS (GC/MS): 238.1 (M⁺°).

3. Addition of cyclic alken-1-yl derivatives

3.1. 1-(1-cyclohexenyl)cyclododecan-1-ol.

Preparation with 1-chloro-1-cyclohexene according to the literature (cf.Marson et al. J. Org. Chem. 1993, 58, 5944-5951, spec. p. 5948; andAdam, Synthesis 1994, 176-180).

¹H-NMR (300 MHz, CDCl₃): 5.62-5.59 (m, 1 H), 2.11-2.01 (m, 4 H),1.66-1.52(m, 8 H), 1.37-1.22 (m, 19 H). ¹³C-NMR (75 MHz, CDCl₃): 142.5(s), 121.1 (d), 76.8 (s), 32.8 (2), 26.5 (2), 26.2, 25.4, 23.9, 23.2,22.5 (2), 22.2 (2), 19.9 (2).

4. Addition of alkynyl derivatives

4.1. 1-Ethynylcyclododecanol from cyclododecanone:

5.5 g of cyclododecanone (30 mmol), precomplexation with 1 g of CeCl₃ (4mmol=0.13 mol equiv.); about 60 mmol of ethynylmagnesium bromide (120 mlof a 0.5 M solution in THF). After 2 h, about 2-5% starting material andabout 90% of a main product, according to GC. Customary work-up gave 5.3g (85%) of a slightly yellowish solid. Recrystallization fromhexane/TBME (9:1, v:v) at 4° C. gives 4.5 g (72%) of colorless,transparent crystals. Ethynylcyclododecanol (technical-grade, GIVAUDAN)was likewise purified by distillation in high vacuum and crystallizationfrom hexane/TBME 9:1 (GC content>97%).

¹H-NMR (300 MHz, CDCl₃): 2.44 (s, 1 H), 2.12 (s, 1 H), 1.91-1.80 (m, 2H), 1.75-1.63 (m, 2 H), 1.60-1.2 (m, 18 H). ¹³C-NMR (75 MHz, CDCl₃):88.5 (s), 71.4 (d), 70.8 (s), 35.8 (2), 26.1 (2), 25.9, 22.5 (2), 22.2(2), 19.6 (2) (6 t).

EI-MS: 208 (1, M⁺°), 190 (15), 175 (4), 161 (10), 147 (20), 133 (25),119 (30), 105 (50), 93 (60), 91 (100), 79 (75), 67 (35), 55 (32).

4.2. 1-Ethynylcyclotridecanol from cyclotridecanone:

¹H-NMR (300 MHz, CDCl₃): 2.44 (s, 1 H), 1.93 (s, 1 H), 1.83-1.67 (m, 4H), 1.53-1.34 (m, 20 H). ¹³C-NMR (75 MHz, CDCl₃): 88.2 (s), 71.3 (d),70.7 (s), 38.8 (2), 27.2 (2), 26.4 (2), 25.4 (2), 25.3 (2), 21.1 (2) (6t). EI-MS: 222(1, M⁺°), 221 (1, M−1), 207(5), 196 (6), 179 (5), 165 (8)161 (7), 151 (15) 137 (20), 123 (36), 109 (45), 97 (50), 68 (100) 55(99).

4.3. 1-(1-Propynyl)cyclododecanol from cyclododecanone:

3.64 g of cyclododecanone (20 mmol), precomplexation with 2 mmol ofCeCl₃ in 30 ml of THF, 30 mmol of 1-propynylmagnesium bromide(corresponding to 60 ml of an approximately 0.5 M solution in THF), onlyslight exothermy. Following customary work-up, 3.8 g (85%) of ayellowish oil (GC content>92%, which crystallized on standing.Purification by Kugelrohr distillation: 3.6 g (81%) of colorless oil,which solidified to become crystalline.

¹H-NMR (300 MHz, CDCl₃): 1.83 (s, 3 H), 1.81-1.48 (m, 5 H), 1.35 (br.s-type m, 18 H). ¹³C-NMR (75 MHz, CDCl₃): 83.8 (s), 79.1 (s), 70.8 (s),36.2 (2), 26.0 (2), 25.8, 22.4 (2), 22.2 (2), 19.7 (2) (6 t) 3.3 (q).EI-MS (GC/MS): 224.1 (0.5, M+2), 223.1 (2, M+1), 222.1 (3, M⁺°), 204.1(30, M−18), 189.0 (8), 175 (9), 161 (18), 147 (32), 98 (62), 95 (90), 91(100), 83 (85), 67 (95), 55 (98).

4.4. 1-(1-Propynyl)cyclotridecanol from cyclotridecanone:

¹H-NMR: 1.83 (s, 3 H), 1.78-1.62 (m, 5 H), 1.50-1.26 (br. s-type m, 20H).

¹³C-NMR (75 MHz, CDCl₃): 83.7 (s), 79.1 (s), 70.9 (s), 39.2 (2), 27.3(2), 26.5(2), 25.4 (2), 25.3 (2), 21.3 (2) (6 t) 3.3 (q). EI-MS (GC/MS):236 (2, M⁺°), 235 (1, M−1), 221 (22), 207 (5), 196 (10), 179 (11), 165(15), 151 (22), 137 (35), 123 (45), 109 (51), 95 (75), 82.5 (100), 67.8(62), 56 (98).

II. Thermo-isomerizations

Apparatus and general procedure:

The tertiary cyclic alcohol was in each case initially introduced into aKugelrohr flask (50 or 100 ml, with two opposite ground-glass necks)together with a small magnetic stirrer. After applying an inert-gas feed(stainless steel capillary fused into standard ground-glass attachments)on the rear ground-glass neck, the flask was attached by the frontground-glass joint to the slightly inclined reactor vessel (quartz glassreactor, internal diameter 25 or 40 mm, length 40 cm, heated withThermolyne tube furnace, 35 cm). At the opposite end of the reactorvessel there was a cool trap (cooling medium liquid nitrogen or dryice/acetone), which was connected to a high-vacuum pump unit. Followingequilibrium of the reactor temperature to 650-660° C. (measured in themiddle of the outside wall of the reactor vessel), evacuation of theentire apparatus and establishment of a pressure of about 1 mbar (1hPa), the flask with the initial charge of alcohol was heated in anairbath (heating mantle of modified Büchi Kugelrohr oven) and thus thestarting material, with stirring, vaporized and distilled through thereactor vessel. In this connection, a precision needle valve was used toestablish a gentle stream of inert gas (nitrogen, according to Vögtlinmodel V100 flowmeter 1-5 l/h) and passed via a capillary through theapparatus. At the reactor outlet, a colorless oil began in each case tocondense shortly afterwards. This was collected in a collection vesselbelow the cool trap, where it partially solidified. After about 15-45min, the starting material was evaporated, in most cases substantiallyresidue-free. After cooling the apparatus, flushing with inert gas, thecondensate was washed out of the cool trap with hexane. All of theyields given are typical average values usually from, in each case, atleast three thermo-isomerizations carried out separately.

A. Unsubstituted Monocyclic Systems

1.1 Cyclotetradecanone from 1-vinylcyclododecanol:

5 g (23.8 mmol) of 1-vinylcyclododecanol, quartz reactor 25/400 mm,temperature 660° C.±10, vaporization at 125-135° C. (airbathtemperature) in about 30 min. Nitrogen stream about 1-2 l/h, vacuum 4-6mbar. The oily condensate began to crystallize in the cool trap already.4.4 g (88% crude yield) of a wax-like solid were obtained which,according to GC and GC/MS analyses, comprises as well as 80-85% of themain component also up to about 5% cyclododecanone and about 5-10% othercomponents which, according to the molecular masses found, aredehydrogenation products. Recrystallization twice from hexane at 0° and−20° C., gave 3.6 g (72%) of cyclotetradecanone (GC purity>98%) ascolorless needles with a melting point of 56° C.

¹H-NMR (300 MHz, CDCl₃): 2.44 (t-type centr. m, 4 H), 1.71-1.32 (m, 4H), 1.29 (br., s-type m, 18 H). ¹³C-NMR (75 MHz, CDCl₃): 212.2 (s),40.9, 26.1, 25.8, 25.35, 25.30, 24.5, 22.9 (7 t, je 2 CH₂). EI-MS(GC/MS): 211.2 (28), 210.2 (27, M⁺°, 152.1 (18), 125.1 (22), 111.1 (28),96.1 (47), 71(96), 55 (100).

The following compounds were prepared in an analogous manner:

1.2. Cyclodecanone from 1-vinylcyclooctanol.

Crude yield 87%.

¹H-NMR (300 MHz, CDCl₃): 2.44 (t-type centr. m, 4 H), 1.71-1.32 (m, 4H), 1.29 (br., s-type m, 10 H). ¹³C-NMR (75 MHz, CDCl₃): 212.2 (s),40.9, 26.1, 25.8, 25.35, 25.30, 24.5, 22.9 (7 t, je 2 CH₂). EI-MS(GC/MS): 156.1 (8), 155.1 (58), 154.0 (75, M⁺°), 125.0 (65), 110.9(100).

1.3. Cyclododecanone from 1-vinylcyclodecanol.

0.5 g (2.7 mmol) of 1-vinyl-1-cyclodecanol (cf. I.1.3, comprises alsoabout 8-10% cyclodecanone), quartz reactor 25/400 mm, temperature 670°C.±10, vaporization at 95-100° C. (airbath temperature) in about 10 min.Nitrogen stream about 2-2.5 l/h, vacuum 5-6 mbar. 0.45 g (90% crudeyield) of a pure white condensate were obtained which partiallycrystallized into small fine needles. According to GC and GC/MSanalyses, the mixture comprises, as main component, about 70%cyclododecanone, as well as 6-8% cyclodecanone and 2-3% startingmaterial. Chromatographic separation of the mixture over silica gel(hexane/TBME 97:3) gave 0.26 g of cyclododecanone (52% isolated yield),which has identical retention times and spectroscopic properties as thecommercially available compound (Fluka).

¹H-NMR (300 MHz, CDCl₃): 2.46 (m_(c), 4 H), 1.71 (m_(c), 4 H), 1.30(br., s-type m, 14 H). ¹³C-NMR (75 MHz, CDCl₃): 214.8 (s), 40.4 (2),24.8 (2), 24.7 (2), 24.3 (2), 22.6 (2), 22.4 (6 t). EI-MS (GC/MS): 183.1(4), 182.1 (10, M⁺°), 139.0 (8), 125.0 (13), 111.0 (25), 98.0 (33),71(35), 55.0 (100).

1.4. Cyclotridecanone from 1-vinylcycloundecanol.

¹H-NMR (300 MHz, CDCl₃): 2.44 (m_(c), 4 H), 1.67 (m_(c), 4 H), 1.31-1.2(br., s-type m, 16 H). ¹³C-NMR (300 MHz, CDCl₃): 212.7 (s), 41.9 (2),26.4 (2), 25.7 (2), 25.6 (2), 24.4 (2), 23.2 (6 t), EI-MS (GC/MS): 198.2(5), 197.1 (33), 196.0 (40, M⁺°), 153.0 (15), 149.0 (25), 138 (30) 125.0(35), 111.0 (35), 98.0 (33), 71(35), 55.0 (100).

1.5. Cyclopentadecanone from 1-vinylcyclotridecanol.

¹H-NMR (300 MHz, CDCl₃): 2.41 (t-type m_(c), 4 H), 1.64 (m_(c), 4 H),1.37-1.30 (br., s-type m, 20 H). ¹³C-NMR (75 MHz, CDCl₃): 212.5 (s),42.0 (2), 27.5 (2), 26.70 (2), 26.66 (2), 26.4 (2), 26.2 (2), 23.4 (2)(7 t). EI-MS (GC/MS): 226.1 (2), 225.1 (8), 224.1 (13, M⁺°), 166.1 (8),149.0 (8), 135 (10) 125.0 (15), 111.0 (18), 98.0 (21), 71(66), 55.0(100).

1.6. Cyclohexadecanone from 1-vinylcyclotetradecanol.

¹H-NMR (300 MHz, CDCl₃): 2.40 (m_(c), 4 H), 1.64 (m_(c), 4 H), 1.32-1.25(br., s-type m, 22 H). ¹³C-NMR (75 MHz, CDCl₃): 212.2 (s), 41.9, 27.5,27.1, 26.9, 26.5 (2), 26.4, 23.3 (8 t). EI-MS (GC/MS): 239.2 (10, M+1),238.1 (43, M⁺°), 223.1 (8), 209.1 (5), 163.0 (12), 149 (18), 135 (28),125.0 (53), 111.0 (45), 98.0 (76), 82.0 (72), 71.0(100), 58.0 (95), 55.0(99).

1.7. Cycloheptadecanone from 1-vinylcyclopentadecanol.

¹H-NMR (300 MHz, CDCl₃): 2.39 (m_(c), 4 H), 1.62 (m_(c), 4 H), 1.32-1.25(br., s-type m, 24 H). ¹³C-NMR (75 MHz, CDCl₃): 212.0 (s), 42.2, 28.1,27.7, 27.5, 27.2, 27.1, 26.8, 23.6, (16 t). EI-MS (GC/MS): 253.2 (4,M+1), 252.1 (20, M⁺°), 237.1 (3), 234.1 (4), 223.1 (4), 210.1 (5), 194.1(6), 163.0 (7), 152 (8), 149.0 (8), 135 (17), 125.0 (32), 111.0 (25),98.0 (58), 82.0 (45), 71.0(100), 58.0 (97), 55.0 (99).

B. Monocyclic Systems Substituted on the Ring Perimeter

1.8. 4-Methylcyclotetradecanone and 2-methylcyclotetradecanone from(syn/anti)-2-methyl-1-vinyl-1-cyclododecanol

0.8 g (4.4 mmol) of 2-methyl-1-vinyl-1-cyclododecanol, quartz reactor25/400 mm, temperature 670° C.±10, vaporization at 120-135° C. (airbathtemperature) in about 15 min. Nitrogen stream about 1.5-2 l/h, vacuum3-5 mbar. 0.7 g (87% crude yield) of a water-clear, substantiallycolorless condensate was obtained, which, according to GC and GC/MSanalysis, comprised, as main component, about 60%4-methylcyclotetradecanone and 5% 2-methylcyclotetradecanone (m/e ineach case 224), as well as 2-8% cyclododecanone and furtherdehydrogenation and fragmentation products. The same type of productswere also obtained with a quartz reactor with a length of 1 m and aninternal diameter of 25 mm at 570° C.±10.

¹H-NMR (300 MHz, CDCl₃) main component A: 2.61-2.24 (m, 4 H), 1.82-0.95(m, 21 H); 0.88 (d, ³J=6.3 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃): 211.9 (s),40.9, 38.9, 32.2, 29.7 (4 t), 29.5 (d), 25.7, 25.6, 25.5, 25.2, 24.9,24.5, 23.1 (8 t), 19.9 (q).

In the ¹H-NMR spectrum of the mixture, the secondary component B(2-methylcyclotetradecanone, ratio about 1:12) can be characterized by adoublet at 1.06 ppm (J=6.7 Hz), and in the ¹³C-NMR spectrum by acarbonyl band at 215 ppm, and a doublet at 45.4 ppm and the quartet at17.0 ppm.

1.9. 3-Methylcycloheptadecanone and 5-methylcycloheptadecanone from(syn/anti)-3-methyl-1-vinyl-1-cyclopentadecanol.

0.5 g (2.1 mmol) of 3-methyl-1-vinyl-1-cyclopentadecanol quartz reactor25/400 mm, temperature 670° C.±10, vaporization at 145-170° C. (airbathtemperature) in about 15 min. Nitrogen stream about 2-2.5 l/h, vacuum5-8 mbar. About 0.4 g of a water-clear, substantially colorlesscondensate was obtained which, according to GC and GC/MS analysis,comprised the two main components (about 34% and 28%)3-methylcycloheptadecanone and 5-methylcycloheptadecanone, both with m/e266), as well as smaller amounts of dehydrogenation and fragmentationproducts.

¹H-NMR spectrum (300 MHz, CDCl₃) of the mixture: 2.51-2.4 (m), 1.7-1.1(m); 0.92 (d, J=6.7 Hz), 0.86 (d, J=6.3 Hz), integral ratio about 1:1.¹³C-NMR (75 MHz, CDCl₃): 211.2, 211.6 (2 s); 31.5 29.0 (2 d); 20.6, 20.1(2 q).

EI-MS (GC/MS) of component A: 266.1 (25, M⁺°), 248.1 (48), 208.1 (12),149.0 (15), 125.0 (19), 109.0 (45), 97.0 (52), 69.0 (76), 55.0 (100). ofcomponent B: 266.1 (30, M⁺°), 251.1 (18), 237.1 (38), 223.0 (15), 208.1(12), 149.0 (10), 125.0 (45), 111.0 (32), 97.0 (53), 85 (72), 69.0 (78),55.0 (100). (cf. II.2.4)

1.10. 4-Ethylcyclotetradecanone from 2-ethyl-1-vinyl-1-cyclododecanol:

1 g (4.2 mmol) of 2-ethyl-1-vinyl-1-cyclododecanol, quartz reactor25/1000 mm, temperature 570° C.±10, vaporization at 135-155° C. (airbathtemperature) in about 15 min. Nitrogen stream about 1.5-2 l/h, vacuum3-5 mbar. 0.8 g (80% crude yield) of a water-clear, colorless condensatewas obtained which, according to GC and GC/MS analysis, comprised, asmain component, more than 60% of 4-ethylcyclotetradecanone and 5% of2-ethylcyclotetradecanone (m/e in each case 238), as well as furtherdehydrogenation and fragmentation products.

¹H-NMR (300 MHz, CDCl₃) 2.65-2.2 (m, 4 H), 1.85-1.10 (m, 23 H); 0.88 (t,³J=7 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃): 212.2 (s); 41.5, 38.3 (2 t);36.5 (d); 29.4,26.3, 26.1, 25.7 (2), 25.6 (2), 25.0, 24.7, 23.6, 22.6(11 t), 11.0 (q). EI-MS (GC/MS): 238.1 (M⁺°).

2.1. (R/S)-3-Methylcyclotetradecanone (normuscone) from(E/Z)-1-(1-propenyl)cyclododecanol.

2.3 g (10.2 mmol) of (E/Z)-1-(1-propenyl)cyclododecanol quartz reactor25/400 mm, temperature 660° C.±10, vaporization at 120-135° C. (airbathtemperature) in about 15 min. Stream of nitrogen about 0.5-1 l/h, vacuum3-5 mbar. 2.0 g (87% crude yield) of a water-clear, substantiallycolorless condensate was obtained which, according to GC and GC/MSanalysis, comprised, as main component, about 45-55%3-methylcyclotetradecanone, as well as 2-8% cyclododecanone and 4-10%starting material and, in smaller amounts, dehydrogenation andfragmentation products. Chromatographic separation of the mixture oversilica gel (hexane/TBME 97:3) gave 0.77 g of 3-methylcyclotetradecanone(33% isolated yield) as colorless oil with a typical musk-like odorwhich gradually crystallizes upon storage in a refrigerator at 4° C.

¹H-NMR (300 MHz, CDCl₃): 2.45-2.36 (m, 3 H; fine analysis reveals 2.43(dd, ²J=15 Hz, ³J=5 Hz, 1 H, H_(a)—C(2)), 2.41 (t, ³J=6.7 Hz, 2 H,H₂—C(14)); 2.19 (dd, ²J=15 Hz, ³J=5 Hz, 1 H, H_(b)—C(2); 2.10 (m_(c), 1H, H—C(3)), 1.64 (m_(c), 2 H, H₂C(13)), 1.37-1.20 (br. m, 18 H); 0.93(d, ³J=6.7 Hz, 3 H, H₃C—C(2)). ¹³C-NMR (75 MHz, CDCl₃): 212.0 (s), 49.5,41.0, 33.7 (3 t), 28.8 (d), 26.3, 26.1, 25.6, 25.4, 25.3, 25.1, 24.7,23.4, 22.3 (9 t), 20.7 (q) MS (GC/MS): 226.2 (2, M+2), 225.1 (13, M+1),224.1 (50, M⁺°), 209.1 (28), 195.1 (30), 181.0 (15), 166.0 (38), 125.0(52), 111.0 (48), 97.0 (50), 85 (100), 71 (52), 55 (51).

2.2. (R/S)-3-Methylcyclopentadecanone (muscone) from(E/Z)-1-(1-propenyl)cyclotridecanol.

2.4 g (10 mmol) of (E/Z)-1-(1-propenyl)cyclotridecanol, quartz reactor25/400 mm, temperature 660° C.±10, vaporization at 140-155° C. (airbathtemperature) in about 15 min. Nitrogen stream about 1.5-2.5 l/h, vacuum4-6 mbar. 1.9 g (79% crude yield) of a water-clear, substantiallycolorless condensate was obtained which, according to GC and GC/MSanalyses, comprises, as main component, about 45-55%3-methylcyclopentadecanone, as well as 2-6% cyclododecanone and 4-10%starting material and, in smaller amounts, dehydrogenation andfragmentation products. Chromatographic separation of the mixture oversilica gel (hexane/TBME 97:3) gave 0.68 g of 3-methylcyclopentadecanone(28% isolated yield) as a colorless oil with characteristic musk-likeodor which has identical retention times and spectroscopic properties toa reference sample of rac. muscone.

¹H-NMR (300 MHz, CDCl₃): 2.46-2.38 (m, 3 H; fine analysis reveals 2.43(d, ²J=15 Hz, H_(a)—C(2)), 2.41 (t, ³J=6.7 Hz, 2 H, H₂—C(15)); 2.17 (dd,²J=15 Hz, ³J=5.2 Hz, 1 H, H_(b)—C(2); 2.04 (m_(c), 1 H, H—C(3)), 1.64(m_(c), 2 H, H₂C(14)), 1.36-1.22 (br., s-type m, 20 H); 0.94 (d, ³J=6.7Hz, 3 H, H₃C—C(2)). ¹³C-NMR (75 MHz, CDCl₃): 212.0 (s), 50.4, 42.1, 35.6(3 t), 29.0 (d), 27.6, 27.1, 26.8, 26.7, 26.6, 26.5, 26.3, 26.2, 25.1,23.0 (10 t), 21.0 (q).MS (GC/MS): 240.2 (3), 239.1 (9), 238.1 (21, M⁺°),223.1 (12), 209.1 (18), 195.1 (5), 180.1 (8), 125.0 (25), 111.0 (18),97.0 (35), 85 (45), 69 (48), 55 (100).

2.3 (R/S)-3-Methylcyclohexadecanone from(E/Z)-1-(1-propenyl)cyclotetradecanol.

Isolated yield 29%.

¹H-NMR (300 MHz, CDCl₃): 2.44-2.36 (m, 3 H); 2.17 (dd, ²J=15 Hz, ³J=5.2Hz, 1 H), 2.07 (m_(c), 1 H), 1.58 (m_(c), 2 H), 1.30-1.22 (m, 22 H);0.93 (d, ³J=6.7 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃): 211.5 (s), 50.1,42.0, 35.4 (3 t), 29.0 (d), 27.4 (2), 26.9, 26.8, 26.5, 26.4, 26.3, 26.2(2), 25.3, 22.8 (11 t), 20.6 (q).MS (GC/MS): 253.1 (33, M+1), 252.1 (52,M⁺°), 223.1 (60), 194.0 (30), 149 (35) 135 (52), 125.0 (88), 111.0 (88),97.0 (30), 69.0 (95), 55.0 (100).

2.4 (R/S) -3-Methylcycloheptadecanone from(E/Z)-1-(1-propenyl)cyclopentadecanol.

Isolated yield 27%.

¹H-NMR (300 MHz, CDCl₃): 2.43-2.35 (m, 3 H); 2.17 (dd, ²J=15 Hz, ³J=5.2Hz, 1 H), 2.04 (m_(c), 1 H), 1.58 (m_(c), 2 H), 1.30-1.22 (m, 24 H);0.94 (d, ³J=6.7 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃): 211.5 (s), 50.3,42.4, 35.8 (3 t), 29.0 (d), 28.0 (2), 27.6, 27.5, 27.3, 27.1, 26.9, 26.8(2), 26.7, 25.7, 23.3 (12 t), 20.6 (q). MS (GC/MS): 267.2 (5, M+1),266.1 (24, M⁺°), 237.1 (12), 136 (13), 125.0 (18), 111.0 (18), 97.0(30), 85.0 (45), 81.0 (42), 69.0 (53), 55.0 (100).

2.5. (R/S)-2-Methylcyclotetradecanone from1-(1-methyl-ethenyl)cyclododecanol.

Isolated yield 70%.

¹H-NMR (300 MHz, CDCl₃): 2.70-2.34 (m, 3 H), 1.81-1.15 (m, 22 H), 1.05(d, J=7 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃): 215.3 (s), 45.6 (d), 38.4,33.0, 26.4 (2), 26.1, 25.7, 25.4, 24.9, 24.8, 24.7, 24.6, 21.8 (12 t),17.2 (q). EI-MS (GC/MS): 226.2 (5, M+2), 225.1 (35, M+1), 224.1 (60,M⁺°), 195.1 (18), 139.0 (30), 111.0 (43), 98.0 (50), 85 (68), 70 (90),55 (100).

2.6. (R/S)-2-Methylcyclotridecanone from1-(1-methylethenyl)-cycloundecanol.

Isolated yield 60%.

¹H-NMR (300 MHz, CDCl₃): 2.70-2.56 (m, 2 H), 2.39-2.29 (m, 1 H),1.86-1.10 (m, 20 H), 1.04 (d, J=6.9 Hz, 3 H). ¹³C-NMR (75 MHz, CDCl₃):215.4 (s), 46.3 (d), 40.3, 33.0, 26.6, 26.3, 26.2, 25.6, 25.0, 24.7,24.4, 24.3, 22.7 (11 t), 17.0 (q). EI-MS (GC/MS): 212.2 (5, M+2), 211.1(33, M+1), 210.1 (45, M⁺°), 181 (33), 153 (35), 139 (32), 111 (34), 97(35), 72 (38), 55 (100).

2.7. 3,3-Dimethylcyclotetradecanone from1-(2-methyl-1-propenyl)cyclododecanol

¹H-NMR (300 MHz, CDCl₃): 2.42-2.38 (t-type m, 2 H), 2.34 (s, 2 H),1.64-1.59 (m, 16 H), 1.55-1.23 (m, 2 H), 1.14-1.09 (m, 2 H), 1.00 (s, 6H). ¹³C-NMR (75 MHz, CDCl₃): 210.4 (s), 51.0, 42.3 (2 t), 41.0 (s),38.8, 33.3 (2 t), 29.5 (2) (q), 27.0, 26.2 (2), 25.6, 25.1, 24.1, 22.6,22.1 (8 t). EI-MS (GC/MS): 239.1 (3), 238.0 (8, M⁺°), 223.1 (5), 125.0(18), 111.0 (22), 97.0 (22), 83 (35), 69 (59), 55 (100).

2-Methyl-2-pentadecen-4-one was identified as second component (29%).

2.8. (cis/trans)-2,3-Dimethylcyclotetradecanone from1-(2-buten-2-yl)cyclododecanol.

¹H-NMR (300 MHz, CDCl₃): 2.86-2.7 (m, 1 H), 2.64-2.48 (m, 2 H), 2.27-1.1(m, 21 H), 1.01 (d, J=6.9 Hz, 3 H), 0.95 (d, J=6.9 Hz, 3 H). ¹³C-NMR (75MHz, CDCl₃): 213.0 (s), 51.0 (d), 38.1 (t), 34.3 (d), 29.3, 27.9, 26.2,25.8, 24.9, 24.8, 24.4, 24.3, 24.1, 20.4 (10 t), 17.4, (q) 8.8(q).EI-MS(GC/MS): 238.1 (35, M⁺°), 223.1 (38), 209.1 (80), 191.1 (34),181.0 (38), 166 (25), 139.0 (100) 125 (80), 111 (85), 98 (88), 83 (95),69 (92), 55 (98).

2.9. 3,4-Dimethylcyclotetradecanone from(E/Z)-2-methyl-1-(1-propen-1-yl)cyclododecanol:

1 g (4.2 mmol) of (E/Z)-2-methyl-1-(1-propen-1-yl)cyclododecanol (cf.I.2.9) comprises about 2-4% 2-methylcyclododecanone), quartz reactor25/1000 mm, temperature 570° C.±10, vaporization at 135-155° C. (airbathtemperature) in about 15 min. Nitrogen stream about 1.5-2 l/h, vacuum3-5 mbar. 0.8 g (80% crude yield) of a water-clear, colorless condensatewere obtained which, according to GC and GC/MS analyses, comprises, asmain components, more than 50% of isomeric3,4-dimethylcyclotetradecanones (no baseline separation) and about 5%2-methylcyclotetradecanone (m/e in each case 238), as well as otherdehydrogenation and fragmentation products.

Diastereomer mixture (cis/trans compounds), characteristic peaks: ¹H-NMR(300 MHz, CDCl₃): 0.84-0.83 (3 d, J=6.5-7 Hz), 0.78 (d, J=6.6Hz).¹³C-NMR (75 MHz, CDCl₃) 211.6/211.3(s); 49.3, 44.9, 41.8,39.8(4 t);34.0, 33.3, 32.6, 31.2 (4 q); 32.8 (t); 28.6-24.4 CH₂ signals (t) notcompletely resolved; 16.7, 16.1, 14.8, 13.4 (4 q).EI-MS (GC/MS): Productpeaks not completely separated, 238.1/238.1 (M⁺°).

B. Bicyclic Systems

3.1. (cis/trans)-Bicyclo[10.4.0]hexadecadecan-2-one from1-(1-cyclohexenyl)cyclododecan-1-ol.

0.5 g of 1-(1-cyclohexenyl)cyclododecan-1-ol (1.9 mmol) was quicklyvaporized at 140-170° C. (reactor temperature 690-700° C.). 0.45 g of aslightly yellow-colored oil were obtained as condensate which, accordingto GC and GC/MS analysis, had as well as others three new mass-isomericmain components with m/e 264 (36, 9 and 12%). Separation of thecomponents by chromatography over silica gel (hexane/TBME 98:2) was onlypartially successful and fractions of varying composition were obtained(partial crystallization).

The isolated crystalline fraction revealed two signals in GC in theratio of about 9:1 (trans/cis isomers).

¹H-NMR (300 MHz, CDCl₃): 2.82-2.70 (m, 1 H), 2.63-2.56 (m, 1 H),2.25-2.12 (m, 1 H), 2.08-1.48 (m, 7 H), 1.47-1.0 (m, 22 H). ¹³C-NMR (75MHz, CDCl₃) Isomer A (main isomer): 213.2 (s), 52.6 (d), 37.9 (t), 37.0(d), 28.4, 26.2, 26.0 25.9, 25.5, 25.0, 24.5 (2), 24.4, 24.1, 24.0,23.5, 21.5, 20.7 (14 t). Isomer B (weak): 215.1 (s), 57.3 (d),38.7(d).EI-MS(GC/MS): 265.1 (35, M+1), 264.1 (58, M⁺°), 246.1 (10), 209(15), 137 (18), 125 (40), 96 (48), 81 (52), 67 (55), 55 (100).

The oily product produced in the same manner was identified ascyclohexen-1-yl undecyl ketone (about 20%, m/e 264).

C. Unsaturated Systems

4.1. Cyclotetradec-2-enone from 1-ethynylcyclododecanol.

2.1 g of 1-ethynylcyclododecanol (9 mmol) was vaporized at 120-135° C.over the course of about 15 min (reactor temperature 660-670° C.). 1.8 gof condensate were isolated which, according to GC/MS analysis, had, aswell as about 10% starting material and about 20% cyclododecanone, twoor more components with m/e 208 as molecular ion signal. Columnchromatography over silica gel (hexane/TBME 98:2) isolated the UV-activemain fraction (0.6 g, 29%) as a colorless oil:

¹H-NMR (300 MHz, CDCl₃): 6.83 (td, J=15.8, 7.4 Hz, 1 H); 6.20 (dtJ=15.8, 1.3 Hz, 1 H); 2.53-2.48 (m, 2 H); 2.30-2.26 (m, 2 H); 1.80-1.67(m, 2 H), 1.58-1.52 (m, 2H), 1.45-1.2 (m, 14 H). ¹³C-NMR (75 MHz,CDCl₃): 202.1 (s), 148.2, 130.3 (2 d), 40.4, 31.4, 26.6, 26.3, 26.2,26.0, 25.8, 25.7, 25.4, 25.0, 24.9 (11 t).EI-MS (GC/MS): 209.1 (5, M+1),208.1 (15, M⁺°), 165 (10), 98 (40), 95 (50), 81 (90), 67 (65), 55 (100).

4.2. Cyclopentadec-2-enone from 1-ethynylcyclotridecanol.

2.0 g of 1-ethynylcyclotridecanol (9 mmol) was vaporized at 125-130° C.over the course of about 15 min (reactor temperature 670-690° C.). 1.8 gof condensate were isolated which, according to GC/MS analysis, had, aswell as about 10% starting material and about 15% cyclotridecanone, twoor more components with m/e 222 as molecular ion signal. Columnchromatography over silica gel (hexane/TBME 98:2) isolated the UV-activemain fraction 0.44 g (22%):

¹H-NMR (300 MHz, CDCl₃): 6.81 (td, J=15.7, 7.5 Hz, 1 H); 6.19 (dtJ=15.7, 1.3 Hz, 1 H); 2.52-2.47 (m, 2 H); 2.30-2.23 (m, 2 H); 1.72-1.44(m, 4H), 1.4-1.2 (m, 16 H). ¹³C-NMR (75 MHz, CDCl₃): 201.7 (s), 147.9,130.7 (2 d), 40.0, 31.6, 26.9, 26.8, 26.7, 26.6 (2), 26.5, 26.2, 26.0,25.4, 25.2 (12 t).EI-MS (GC/MS): 223.1 (5, M+1), 222.1 (15, M⁺°), 164(10), 109 (50), 96 (52), 95 (50), 81 (80), 68 (55), 55 (100).

4.3. (E/Z)-3-Methylcyclopentadec-2-en-1-one from1-(1-propynyl)cyclotridecanol.

0.8 g of 1-(1-propynyl)cyclododecanol (3.3 mmol) was vaporized at130-140° C. (reactor temperature 660-670° C.), giving 0.5 g ofcondensate as a yellowish oil. GC and GC-MS analysis revealed a complexproduct mixture which comprised, as well as about 12% cyclotridecanone(m/e 196), about 15-20% alkene fractions (m/e 218), inter alia threefractions (about 18, 15, 11%) with mass-someric molecular ion peaks (m/e236). Using chromatography over silica gel (hexane/TBME 98:2) it waspossible, after separating off the alkene fraction, to separate off partof the ketone fraction eluted first (colorless oil):

¹H-NMR (300 MHz, CDCl₃): 6.09 (br. s, 1H), 2.76 (t, J=6.8 Hz, 2 H),2.46-2.35 (m, 2 H), 1.86 (d, J=1.3 Hz, 3 H), 1.74-1.2 (m, 20 H. ¹H-NMR(75 MHz, CDCl₃): 201.8 (s), 158.4 (s), 125.0 (d), 41.8 (t), 31.6, 29.3,27.0, 26.9, 26.8, 26.7, 26.5, 26.3, 26.1, 25.3, (10 t) 25.1 (q), 23.8(t). EI-MS (GC/MS): 237.1 (5, M+1), 236.0 (18, M⁺°), 221.0 (12), 123.0(13), 109 (46), 98 (87), 95 (100), 83 (90), 67 (52), 55 (80).

The following product fractions not sufficiently separated by columnchromatography over silica gel were purified. Catalytic hydrogenation ofthis mixture with palladium (10%) on activated carbon in ethyl acetateand subsequent renewed column chromatography over silica gel(hexane/TBME 98:2) gave three main fractions, one of which (0.15 g, 19%)proved to be identical to 3-methylcyclopentadecanone (muscone) by GC,GC/MS analyses and NMR spectroscopy (cf. II.2.2.). The other compounds(content about 10 and 15%) were identified as cyclotridecanone andhexadecan-4-one.

4.4. (E/Z)-3-Methylcyclotetradec-2-en-1-one from1-(1-propynyl)cyclododecanol.

1.1 g of 1-(1-propynyl)cyclododecanol (5 mmol) was vaporized at 130-140°C. (reactor temperature 660-680° C.), giving 0.9 g of condensate as ayellowish oil. GC and GC-MS analysis revealed a complex product mixturewhich, as well as about 15% cyclododecanone (m/e 182), had about 15-20%alkene fractions (m/e 204), inter alia three fractions (about 25, 20,15%) with mass isomeric molecular ion peaks (m/e 222).

¹H-NMR spectrum of this mixture: 6.21 (s), 6.09 (s), 2.78 (t, J=6.8 Hz),2.6-2.35 (m), 2.13 (d, J=1 Hz), 2.02 (s), 1.95-1.15 (m), 0.88 (t, J=6.8Hz).

Catalytic hydrogenation of this mixture with palladium (10%) overactivated carbon in ethyl acetate and subsequent column chromatographyover silica gel (hexane/TBME 98:2) gave two main fractions, one of which(0.35 g, 32%) proved to be identical to 3-methylcyclotetradecanone byGC, GC/MS analyses and NMR spectroscopy. The second product (contentabout 15%) was identified as pentadecan-4-one.

5.1. (R/S)-3-Methylcyclotetradecanone from(E/Z)-1-(trimethyl-silyloxy)-1-(1-propenyl)cyclododecanol and subsequenthydrolysis of the cyclic trimethylsilyl enol ether intermediate:

1.5 g of (E/Z)-1-propen-1-yl-1-trimethylsilyloxycyclododecane (5 mmol,E:Z-isomer ratio according to ¹H-NMR and GC about 3:2) were vaporized at120-130° C. within 15 min (reactor temperature 660-670° C.). 1.3 g ofcondensate (86%) as colorless oil. According to GC/MS analyses, reactionabout 90%, were, as well as a total of about 30-40% alkene fractions(desilylation, M⁺°=206) with about 25 and 15% in each case two newbroadened product signal pairs with m/e 296 (M⁺°, trimethylsilyl enolether isomers) were observed.

EI-MS: 297.2 (5), 296.2 (15, M⁺°), 281.2 (20), 253.1 (10), 197.0 (18),169.0 (60), 73.0 (100).

The resulting crude condensate was dissolved in 20 ml of THF and, withstirring, treated with a few drops of dilute sulfuric acid and a diluteaqueous potassium fluoride solution. After stirring overnight, themixture was poured onto water, extracted with hexane, andchromatographed after customary work-up over silica gel (hexane/TBME97:3). As well as a UV-active prefraction (alkene fraction), 0.42 g(28%) of a colorless oil are obtained, which prove to be identical tothe 3-methylcyclo-tetradecanone already prepared previously, by GC,GC/MS analyses and NMR-spectroscopy.

1. A method for producing macrocyclic ketones of the formula Ia; or Ib

wherein R¹, R², and R³ are independently hydrogen, or a C₁ to C₆ alkylgroup; or R¹, R², and R³ are independently hydrogen, or a C₁ to C₆ alkylgroup, and R¹ and R² or R² and R³ form together with the carbon atom(s)to which they are attached a ring; R⁴ is hydrogen, a linear or branchedC₁ to C₄ alkyl group; and n is an integer of 7 to 14; comprising thesteps: (a) converting to 100° C.-300° C. into the gas phase a compoundof formula IIa or formula IIb

wherein R¹, R², R³, R⁴, and n have the same meanings as above; and R⁵ iseither hydrogen or a trialkylsilyl group or an alkali metal cation; and(b) heating the compound of formula IIa or formula IIb, converted intothe gas phase under (a), to temperatures of from 500° C. to 700° C., and(c) if R⁵ is a trialkylsilyl group, hydrolysis of the trialkylsilylether resulting under (b) into the corresponding ketone of the formulaIa or Ib.
 2. The method according to claim 1, wherein R¹, R², and R³ areindependently hydrogen or methyl and at least one of R¹, R², and R³ ismethyl.
 3. The method according to claim 1, wherein the compound offormula IIa or the compound of formula IIb is dissolved in an inertsolvent prior to the converted into the gas phase.
 4. The methodaccording to claim 1, wherein the compound of formula IIa or thecompound of formula IIb is converted into the gas phase continuously. 5.The method according to claim 1, wherein the compound of formula IIa orthe compound of formula IIb is converted into the gas phase at 120°C.-250° C.
 6. The method according to claim 1, wherein an inert gas isadded to the gas phase of (a).
 7. The method according to claim 1,wherein the heating temperature of (b) is from 600° C. to 670° C.
 8. Acompound selected from the group consisting of:3-methylcycloheptadecanone, 5-methylcycloheptadecanone,4-ethylcyclotetradecanone, and 3,4-dimethylcyclotetradecanone.
 9. Amethod for producing a compound of formula IIa or a compound of formulaIIb

wherein R¹, R², and R³ are independently hydrogen, or a C₁ to C₆ alkylgroup; or R¹, R², and R³ are independently hydrogen, or a C₁ to C₆ alkylgroup, and R¹ and R² or R² and R³ form together with the carbon atom(s)to which they are attached a ring; R⁴ is hydrogen, a linear or branchedC₁ to C₄ alkyl group; n is an integer of 7 to 14; and R⁵ is hydrogen, atrialkylsilyl group, or an alkali metal cation; comprising the step of(a) precomplexation of a macrocyclic ketone with an anhydrous Lewis acidat temperatures of from 0° C. to 40° C., and (b) subsequent addition oforganometallic alkylene compounds onto the precomplexed macrocyclicketones under Grignard conditions.
 10. A compound selected from thegroup consisting of: 1-vinyl-1-cycloundecanol,1-vinyl-1-cyclotridecanol, 1-vinyl-1-cyclotetradecanol,1-vinyl-1-cyclopentadecanol,(syn/anti)-2-methyl-1-vinyl-1-cyclododecanol,(syn/anti)-2-ethyl-1-vinyl-1-cyclododecanol,(syn/anti)-3-methyl-1-vinyl-1-cyclopentadecanol,(E/Z)-1-(1-propen-1-yl)cyclododecanol,(E/Z)-1-(1-propenyl)cyclotridecanol,(E/Z)-1-(1-propenyl)cyclotetradecanol,(E/Z)-1-(1-propen-1-yl)cyclopentridecanol, 1-(1-methyltethenyl)cycloundecanol, 1-(2-methyl-1-propenyl)cyclododecanol,(E/Z)-1-(2-buten-2-yl)cyclododecanol,(E/Z)-1-(trimethylsilyloxy)-1-(1-propenyl)cyclododecanol), and(E/Z)-2-methyl-1-(1-propen-1-yl)cyclododecanol.
 11. A compound selectedfrom the group consisting of 1-ethynylcyclotridecanol, and1-(1-propynyl)cyclododecanol.